Test 4: DTH and Transplant Flashcards
What is contact dermatitis caused by?
CD4+ TH1 cell-mediated hypersensitivity
When is contact dermatitis elicited?
Second skin exposure to allergen (first sensitized–>TH1 differentiation)
What are some common dental allergens?
- liquid monomer acrylic
- proteins in latex
- accelerators in rubber latex
Are all contact allergens natural proteins?
No, some are artificial chemicals and not all proteins
How to contact allergens become immunogenic?
-act as haptens attaching to carrier self-protein which is then taken up by Langerhans cells on skin and recognized as foreign particle
What are some characteristics of the inflammatory response from DTH?
- post capillary venules surrounded by lymphocytes
- blistering and necrosis of epidermal cells
- pruritic
- edema
- infiltrated by basophils and eosinophils
How is the immunological diagnosis determined?
Patch Test
How is contact dermatitis treated?
Systemic Corticosteroids
What is the major stimulus to transplant rejection?
Incompatability of MHC molecules (proteins from MHCs)
What is the difference between Autografts, syngenic grafts, allografts, and xenogenic grafts?
- Auto: from the same person
- syngenic: from identical twin
- Allograft: From different person
- Xenograft: from different species
How many T cells can directly recognize and foreign MHC molecule?
2%
When the allogenic MHC molecules are DIRECTLY presented by graft APCs, what cells are stimulated?
CD4 and CD8 (nucleated allogenic graft cells have MHC I)
How are allogenic MHC molecules INDIRECTLY presented?
Recipient APCs phagocytose remnants of allogenic MHC molecules and present them to CD4 cells
What type of graft rejection is characterized by hemorrhage and thrombotic occlusion, mediated by pre-exisiting Abs in host, and begins within minutes/hours?
Hyperacute rejection
What is the major obstacle of xenografts?
Natural antibodies to other species’ cells
What two things are tested before transplants?
ABO incompatability and Abs against allogenic MHCs
Which T cell is more important in Acute rejection and why?
CD8+, epithelial cells from vascularized grafts present MHC I molecules–>vascular and parenchymal injury and necrosis
What is the major cause of graft rejection?
Chronic rejection , months to years later (used to be acute, but immunosuppressant drugs helped)
In chronic rejection, what causes the arteriosclerosis in graft tissue?
Proliferation of intimal smooth muscle cells
What causes the Smooth muscle cell growth?
lymphocytes activate macrophages (IFN-gamma) which secrete smooth muscle cell growth factor
What causes fibrosis of the graft in chronic rejection?
Macrophages secrete mesenchymal cell growth factors–>fibroblasts and collagen
Which MHC loci are important for transplant matching?
HLA-A and HLA-B, HLA-DR most important
What is the highest number of molecule matches that still predict poor survival?
4
In two-way mixed lymphocyte reaction (MLR), what is the indicator that the lymphocytes are incompatible?
radio-labeled DNA used for clonal expansion–>DNA synthesis by both
How is One-way MLR different from Two-way?
One set of leukocytes is blocked from synthesizing DNA
What is used for the low resolution Lymphocytotoxicity test?
Anti-sera from a woman that has many pregnancies (expresses many different Abs) that will kill cells if they have the same HLA specificity
What does Molecular HLA typing detect?
polymorphic nucleotide sequences
What is the most important immunosuppressive drug and what is its major action?
Cyclosporin: inhibits transcription of genes for cytokines (IL-2 which causes proliferation of T cells)
What does TGF-beta do?
-generalized immunosuppressive cytokine
What is the major drawback of cyclosporin?
Renal toxicity (also gingival hyperplasia)
What can be used as a substitute for Cyclosporin?
FK506=Tacrolimus; less renal toxicity
What drug has a synergistic effect with cyclosporin?
Rapamycin/Sirolimus (inhibits a kinase involved in IL-2 signalling)
What makes Mycophenolate Mofetil lymphocyte specific?
It blocks de novo synthesis of purines: lymphocytes rely on this more than other cells
Immunological effects of corticosteroids
- reduced number of MHC II molecules
- inhibit T cell activation
- inhibit T cell migration and release of IFN-gamma (macrophage activation)
How do corticosteroids affect inflammation?
- stops cytokine and NO
- reduces emigration of lymphocytes
- induces apoptosis of lymphocytes and eosinophils
What are two commonlyused corticosteroids?
Prednisone and methyl-prednisone
What is the most commonly transplanted tissue? Organ?
Tissue=cornea
Organ=kidney
How long do recipients of kidney transplants have to be on immunosupressive therapy?
Their whole lives
Why is immunosuppressive therapy needed even with an identical twin donor?
subtle differences in minor histocompatability immunogens
When would you need a bone marrow transplant?
SCID, Aplastic anemia, Leukemia and anemia
Where do the donor stem cells come from?
- iliac crest
- peripheral stem cells
What does the recipient need to have done before receiving a bone marrow transplant?
ablation of all lymphocytes
How can you tell that a bone marrow transplant was successful?
peripheral leukocytes and mature PMNs in a few weeks
What happens in Graft Vs Host Disease (GVHD)?
Graft cells recognize the recipient cells as foreign (can be good with leukemia–will attack those cells)
Where can GVHD be manifested?
Skin and mucous membranes
Liver
Small intestinal epithelia
